Hepatitis C Medication

Updated: Jan 29, 2018
  • Author: Vinod K Dhawan, MD, FACP, FRCPC, FIDSA; Chief Editor: BS Anand, MD  more...
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Medication

Medication Summary

The treatment of chronic hepatitis C has evolved rapidly. The backbone of treatment for chronic hepatitis C virus (HCV) infection regardless of genotype was combination therapy with injectable pegylated interferon-alfa (PEG-IFNa) plus oral ribavirin. Because it has the poorest safety profile of all the HCV antivirals, with few exceptions PEG-IFN is no longer recommended in combination regimens. Ribavirin continues to be used in combination with sofosbuvir alone or other combinations.

The direct-acting antiviral agents (DAAs), first introduced in 2011, offered enhanced efficacy when combined with both PEG-IFN and ribavirin, particularly for genotype 1 infections. The first protease inhibitors, boceprevir and telaprevir, are no longer available for use in the United States and have been supplanted by antivirals with greater efficacy and improved safety profiles.

There are three classes of approved DAAs: NS3/4A protease inhibitors, NS5A inhibitors, and polymerase inhibitors (nonnucleoside inhibitors and nucleotide inhibitors). The particular combination of antivirals is determined by genotype. Several novel agents are only available as a fixed-dose combination. The following combinations are currently available:

  • Ledispasvir/sofosbuvir (Harvoni)
  • Elbasvir/grazoprevir (Zepatier)
  • Ombitasvir/paritaprevir/Ritonavir/Dasabuvir (Viekira Pak)
  • Ombitasvir/paritaprevir/Ritonavir (Technivie)
  • Sofosbuvir/velpatasvir (Epclusa): Combination therapy is required because monotherapy with either agent is not efficacious.

Although quite effective, regimens for the treatment of hepatitis C remain very expensive. In a study of treatment-naïve US veterans with genotype 1 HCV, ombitasvir-based therapy was considered to be the most economically efficient strategy. [131]

 

 

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HCV Protease Inhibitors

Class Summary

These agents interfere with HCV replication by inhibiting a key viral enzyme, NS3/4A serine protease.

Simeprevir (Olysio)

Simeprevir inhibits HCV NS3/4A protease needed for proteolytic cleavage of the HCV-encoded polyprotein into mature forms. It is indicated for the treatment of chronic hepatitis C genotypes 1 and 4 infection in combination with peginterferon alfa and ribavirin. For genotype 1a, it may be prescribed as an all-oral regimen in combination with sofosbuvir.

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HCV Polymerase Inhibitors

Class Summary

HCV NS5B polymerase plays an essential role in HCV replication.

Sofosbuvir (Sovaldi)

Sofosbuvir is a NS5B polymerase inhibitor that results in suppression of HCV replication and interrupts HCV life cycle. It is indicated for the treatment of CHC infection genotypes 1, 2, 3, and 4 as part of a combination antiviral regimen, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) to prevent HCV recurrence and those with HCV/HIV-1 coinfection.

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HCV NS5A Inhibitors

Class Summary

NS5A is integral for HCV RNA viral replication.

Daclatasvir (Daklinza)

Daclatasvir inhibits NS5A, a nonstructural protein encoded by HCV. It binds to the N-terminus within domain 1 of NS5A, which may cause structural distortions that interfere with NS5A functions, and thereby inhibits both viral RNA replication and virion assembly. It is indicated for use with sofosbuvir for chronic HCV genotypes 1 and 3 infection. Depending on the genotype and other variables (eg, presence of cirrhosis, post liver transplantation), the regimen may also include ribavirin.

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Combination Products

Class Summary

Several combination products have been approved and additional ones are being investigated to provide all oral regimens with high degrees of efficacy.

Ledipasvir/sofosbuvir (Harvoni)

Ledipasvir inhibits HCV NS5A protein, which is required for viral replication. Sofosbuvir is an inhibitor of HCV NS5B RNA-dependent polymerase. The oral combination is indicated for treatment of adults with chronic hepatitis C infection with genotype 1, 4, 5, or 6. Duration of therapy ranges from 8 to 24 weeks and depends on if the patient is treatment-naïve or experienced, and if cirrhosis is evident.

Ombitasvir/paritaprevir/ritonavir & dasabuvir (Viekira Pak)

This product is indicated for the treatment of chronic HCV genotype 1 infection, including patients with compensated cirrhosis; may be used for patients with HCV/HIV-1 coinfection. It is used in combination with ribavirin in certain patient populations (ie, genotype 1a, with or without cirrhosis; genotype 1b, with cirrhosis). Ombitasvir inhibits HCV NS5A, which is required for viral replication. Paritaprevir is a NS3/4A serine protease inhibitor. NS3/4A protease is needed for proteolytic cleavage of the HCV-encoded polyprotein into mature forms. Ritonavir is a protease inhibitor that is used as a "boosting agent" to increase paritaprevir serum levels. Dasabuvir is a nonnucleoside NS5B RNA-dependent polymerase inhibitor. It's inhibition, in turn, suppresses viral replication.

Ombitasvir/paritaprevir/ritonavir (Technivie)

Ombitasvir/paritaprevir/ritonavir is indicated in combination with ribavirin for genotype 4 chronic HCV infection without cirrhosis. Ombitasvir inhibits HCV NS5A, which is required for viral replication. Paritaprevir is a NS3/4A serine protease inhibitor. NS3/4A protease is needed for proteolytic cleavage of the HCV-encoded polyprotein into mature forms. Ritonavir is a protease inhibitor that is used as a "boosting agent" to increase paritaprevir serum levels.

Elbasvir/grazoprevir (Zepatier)

Elbasvir is an inhibitor of HCV NS5A, which is essential for viral RNA replication and virion assembly. Grazoprevir is an inhibitor of HCV NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV-encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins) and is essential for viral replication. It is indicated with or without ribavirin for the treatment of adults with chronic HCV genotypes 1 or 4 infection.

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Interferons and ribavirin

Class Summary

Interferons are naturally produced proteins with antiviral, antitumoral, and immunomodulatory actions. Interferons alfa, beta, and gamma may be given topically, systemically, and intralesionally. Interferons are immunomodulators that may shorten the clinical course, prevent complications, prevent latent and/or subsequent recurrences, decrease transmission, and eliminate established latency.

Interferon alfa-2b (Intron-A)

IFN alfa-2b is a protein product manufactured by recombinant DNA technology. The adult dosage is 3 million units subcutaneously (SC) 3 times weekly. Modulation of host immune response by IFN may play an important role in the treatment of viral diseases.

Peginterferon alfa-2b (PEG-Intron, Sylatron)

PEG-IFN consists of IFN alfa-2b attached to a single 12-kd PEG chain. It is excreted by the kidneys. PEG-IFN has sustained absorption, a slower rate of clearance, and a longer half-life than unmodified IFN, which permits more convenient once-weekly dosing and significantly improves the quality of life for patients. The adult dose is 1.5 mcg/kg SC.

Pegylated interferon alfa-2a (Pegasys)

PEG-IFN alfa-2a consists of IFN alfa-2a attached to a 40-kd branched PEG molecule. It is predominantly metabolized by the liver. The adult dosage is 180 mcg/kg SC once weekly.

Ribavirin (Rebetol, Virazole, Copegus, Moderiba, Ribasphere)

Ribavirin is an antiviral nucleoside analogue. Its chemical name is D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. Given alone, ribavirin has little effect on the course of hepatitis C. Given with IFN, it significantly augments the rate of sustained virologic response. The adult dosage is 10.6 mg/kg orally once daily or in 2 divided doses.

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Thrombopoietin-Receptor Agonists

Class Summary

These agents directly stimulate bone marrow platelet production to provide stable platelet counts to allow therapy with interferons.

Eltrombopag (Promacta)

Oral thrombopoietin (TPO) receptor agonist. Interacts with transmembrane domain of human TPO receptor and induces megakaryocyte proliferation and differentiation from bone marrow progenitor cells. This agent is indicated for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy.

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